2024
Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality
Gygi J, Maguire C, Patel R, Shinde P, Konstorum A, Shannon C, Xu L, Hoch A, Jayavelu N, Haddad E, Network I, Reed E, Kraft M, McComsey G, Metcalf J, Ozonoff A, Esserman D, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier C, Steen H, Altman M, Montgomery R, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen K, Fragiadakis G, Becker P, Sekaly R, Ehrlich L, Fourati S, Peters B, Kleinstein S, Guan L. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality. Journal Of Clinical Investigation 2024, 134: e176640. PMID: 38690733, PMCID: PMC11060740, DOI: 10.1172/jci176640.Peer-Reviewed Original ResearchConceptsClinical outcomesImmune cascadeElevated levels of inflammatory cytokinesDisease severityLevels of inflammatory cytokinesFormation of neutrophil extracellular trapsAcute COVID-19 severityCritically ill patientsNeutrophil extracellular trapsDevelopment of therapiesCOVID-19 cohortCOVID-19 severityViral clearanceImmunosuppressive metabolitesDeep immunophenotypingMultiomic modelIFN-stimulated genesImmunophenotypic assessmentB cellsDisease courseEarly upregulationInflammatory cytokinesDisease progressionIFN inhibitorsExtracellular trapsHost-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Phan H, Tsitsiklis A, Maguire C, Haddad E, Becker P, Kim-Schulze S, Lee B, Chen J, Hoch A, Pickering H, van Zalm P, Altman M, Augustine A, Calfee C, Bosinger S, Cairns C, Eckalbar W, Guan L, Jayavelu N, Kleinstein S, Krammer F, Maecker H, Ozonoff A, Peters B, Rouphael N, Montgomery R, Reed E, Schaenman J, Steen H, Levy O, Diray-Arce J, Langelier C, Erle D, Hendrickson C, Kangelaris K, Nguyen V, Lee D, Chak S, Ghale R, Gonzalez A, Jauregui A, Leroux C, Altamirano L, Rashid A, Willmore A, Woodruff P, Krummel M, Carrillo S, Ward A, Patel R, Wilson M, Dandekar R, Alvarenga B, Rajan J, Schroeder A, Fragiadakis G, Mick E, Guerrero Y, Love C, Maliskova L, Adkisson M, Ehrlich L, Melamed E, Rousseau J, Hurley K, Geltman J, Siles N, Rogers J, Kutzler M, Bernui M, Cusimano G, Connors J, Woloszczuk K, Joyner D, Edwards C, Lin E, Melnyk N, Powell D, Kim J, Goonewardene I, Simmons B, Smith C, Martens M, Croen B, Semenza N, Bell M, Furukawa S, McLin R, Tegos G, Rogowski B, Mege N, Ulring K, Holland S, Rosen L, Lee S, Vaysman T, Fernandez-Sesma A, Simon V, Van Bakel H, Gonzalez-Reiche A, Qi J, Carreño J, Singh G, Raskin A, Tcheou J, Khalil Z, van de Guchte A, Farrugia K, Khan Z, Kelly G, Srivastava K, Eaker L, Bermúdez González M, Mulder L, Beach K, Fatou B, Smolen K, Viode A, van Haren S, Jha M, Kho A, Milliren C, Chang A, McEnaney K, Barton B, Lentucci C, Murphy M, Saluvan M, Shaheen T, Liu S, Syphurs C, Albert M, Hayati A, Bryant R, Abraham J, Salehi-Rad R, Rivera A, Sen S, Elashoff D, Ward D, Presnell S, Kohr B, Arnett A, Boddapati A, Tharp G, Pellegrini K, Johnson B, Panganiban B, Huerta C, Anderson E, Samaha H, Sevransky J, Bristow L, Beagle E, Cowan D, Hamilton S, Hodder T, Esserman D, Brito A, Rothman J, Grubaugh N, Ko A, Hafler D, Shaw A, Gygi J, Pawar S, Konstorum A, Chen E, Cotsapas C, Wang X, Xu L, Dela Cruz C, Iwasaki A, Mohanty S, Nelson A, Zhao Y, Farhadian S, Asashima H, Pulendran B, Nadeau R, Rosenberg-Hasson Y, Leipold M, Sigal N, Rogers A, Fernandez A, Manohar M, Do E, Chang I, Vita R, Westendorf K, Corry D, Kheradmand F, Song L, Nelson E, Baden L, Mendez K, Lasky-Su J, Tong A, Rooks R, Sekaly R, Fourati S, McComsey G, Harris P, Sieg S, Ribeiro S, Overton J, Rahman A, Hutton S, Michelotti G, Wong K, Seyfert-Margolis V, Metcalf J, Agudelo Higuita N, Sinko L, Booth J, Messer W, Hough C, Siegel S, Sullivan P, Lu Z, Kraft M, Bime C, Mosier J, Erickson H, Schunk R, Kimura H, Conway M, Atkinson M, Brakenridge S, Ungaro R, Manning B, Oberhaus J, Guirgis F, Borresen B, Anderson M. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Science Translational Medicine 2024, 16: eadj5154. PMID: 38630846, DOI: 10.1126/scitranslmed.adj5154.Peer-Reviewed Original ResearchConceptsPro-inflammatory genesViral clearanceUpper airwayImmune signaling pathwaysInduction of pro-inflammatory genesBiomarkers of disease severityDelayed viral clearanceImpaired viral clearanceSevere coronavirus disease 2019B cell populationsAge-dependent up-regulationExpression of pro-inflammatory genesHost immune responseSignaling pathwayType I interferon gene expressionCOVID-19 immunopathologyInnate immune signaling pathwaysSerum chemokinesAge-dependent impairmentNaive TMulticenter cohortNasal transcriptomeAcute respiratory syndrome coronavirus 2Monocyte populationsSerum protein profiles
2021
Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signs
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesProfiling cellular heterogeneity in asthma with single cell multiparameter CyTOF
Stewart E, Wang X, Chupp GL, Montgomery RR. Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF. Journal Of Leukocyte Biology 2020, 108: 1555-1564. PMID: 32911570, PMCID: PMC8087109, DOI: 10.1002/jlb.5ma0720-770rr.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAsthmaFemaleHumansLymphocytesMacrophagesMaleMiddle AgedNeutrophilsSingle-Cell AnalysisSputumConceptsAirway immune cellsSource of inflammationChronic inflammatory diseaseInflammatory cell typesStudy of pathogenesisMultiple distinct subtypesHeterogeneity of diseaseBronchial epithelial cellsAirway inflammationCell typesAsthmatic patientsClinical responseEosinophilic infiltrateAnalysis of sputumAsthmatic inflammationFunctional statusClinical managementImmune cellsInflammatory diseasesHealthy controlsInflammatory responseAirway cellsSputumDistinct subtypesInflammationSingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
2019
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Mensah KA, Chen JW, Schickel JN, Isnardi I, Yamakawa N, Vega-Loza A, Anolik JH, Gatti RA, Gelfand EW, Montgomery RR, Horowitz MC, Craft JE, Meffre E. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 2019, 11 PMID: 31748230, PMCID: PMC7167286, DOI: 10.1126/scitranslmed.aaw4626.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisB cellsHealthy donor controlsGroup of patientsHumanized mouse modelImmature B cellsGene segment usageErosive diseaseRA pathophysiologyBone erosionBone lossBone resorptionHigh prevalenceRANKL productionBone densityMouse modelReceptor activatorBone marrowPatientsDonor controlsCD21Segment usageArthritisElevated frequencyAtaxia telangiectasiaDevelopment of a 2-dimensional atlas of the human kidney with imaging mass cytometry
Singh N, Avigan ZM, Kliegel JA, Shuch BM, Montgomery RR, Moeckel GW, Cantley LG. Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry. JCI Insight 2019, 4: e129477. PMID: 31217358, PMCID: PMC6629112, DOI: 10.1172/jci.insight.129477.Peer-Reviewed Original ResearchConceptsCell typesIndividual cell typesCritical baseline dataRenal cell typesMass cytometryQuantitative atlasNormal human samplesHuman kidneyRelative abundanceDevelopment of therapiesHuman kidney diseaseKidney diseaseMetal-conjugated antibodiesQuantitative interrogationScarce samplesMachine-learning pipelineDiscovery purposesFuture quantitative analysisNovel abnormalityNormal human kidneySingle tissue sectionHuman samplesRenal biopsyImmune cellsCellsTranscriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults
Park H, Shin MS, Kim M, Bilsborrow JB, Mohanty S, Montgomery RR, Shaw AC, You S, Kang I. Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults. Aging Cell 2019, 18: e12960. PMID: 31044512, PMCID: PMC6612637, DOI: 10.1111/acel.12960.Peer-Reviewed Original ResearchConceptsPeripheral blood cellsPeripheral blood mononuclear cellsEffector memory CD8Influenza vaccine responsesEM CD8T cellsIL-7RαMemory CD8Vaccine responsesBlood cellsOlder adultsIL-7 receptor alphaSignature genesBlood mononuclear cellsHuman peripheral whole bloodAge-associated expansionPeripheral whole bloodGene expression profilesAge-associated changesMeta-analysis studyGlobal transcriptomic profilesMononuclear cellsCD8Receptor alphaExpression profiles
2017
West Nile Virus Seroprevalence, Connecticut, USA, 2000–2014 - Volume 23, Number 4—April 2017 - Emerging Infectious Diseases journal - CDC
Cahill ME, Yao Y, Nock D, Armstrong PM, Andreadis TG, Diuk-Wasser MA, Montgomery RR. West Nile Virus Seroprevalence, Connecticut, USA, 2000–2014 - Volume 23, Number 4—April 2017 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2017, 23: 708-710. PMID: 28322715, PMCID: PMC5367428, DOI: 10.3201/eid2304.161669.Peer-Reviewed Original ResearchThe natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection
Yao Y, Strauss-Albee DM, Zhou JQ, Malawista A, Garcia MN, Murray KO, Blish CA, Montgomery RR. The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection. PLOS ONE 2017, 12: e0172625. PMID: 28235099, PMCID: PMC5325267, DOI: 10.1371/journal.pone.0172625.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntigens, CDAsymptomatic DiseasesFemaleGene Expression RegulationHumansImmunity, InnateImmunophenotypingInterferon-gammaKiller Cells, NaturalLymphocyte ActivationLymphocyte CountMiddle AgedNatural Cytotoxicity Triggering Receptor 1Natural Cytotoxicity Triggering Receptor 2Natural Cytotoxicity Triggering Receptor 3NK Cell Lectin-Like Receptor Subfamily CNK Cell Lectin-Like Receptor Subfamily KPrimary Cell CultureSeverity of Illness IndexWest Nile FeverWest Nile virusConceptsNK cell subsetsNK cellsWest Nile virusWNV infectionCell subsetsCell responsesSpecific NK cell subsetsNatural killer cell responsesInnate NK cellsSevere neuroinvasive diseaseNK cell responsesNK cell receptorsNile virusHuman WNV infectionsImmune pathogenesisNK repertoirePolyfunctional responsesMore IFNSymptomatic infectionChemokine secretionAsymptomatic infectionNeuroinvasive diseasePrior historyCytolytic activityInfectionMultiparameter Single Cell Profiling of Airway Inflammatory Cells
Yao Y, Welp T, Liu Q, Niu N, Wang X, Britto CJ, Krishnaswamy S, Chupp G, Montgomery RR. Multiparameter Single Cell Profiling of Airway Inflammatory Cells. Cytometry Part B Clinical Cytometry 2017, 92: 12-20. PMID: 27807928, PMCID: PMC5250532, DOI: 10.1002/cyto.b.21491.Peer-Reviewed Original ResearchConceptsSingle-cell methodsComplex trait diseasesSubgroup of asthmaticsSingle-cell analysisMultiparameter single cell analysisMillions of patientsTranscriptional analysisImmunologic underpinningsInduced sputumAirway diseaseAsthmatic patientsAirway samplesCell subsetsImmune statusFunctional statusClinical severityDistinct biologic mechanismsTreatment successPhysiologic manifestationsBiologic mechanismsCystic fibrosisCellular analysisPatientsCytometry studiesU.S. population
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesAssociation between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis
Das R, Loughran K, Murchison C, Qian F, Leng L, Song Y, Montgomery RR, Loeb M, Bucala R. Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis. Cytokine 2015, 78: 51-54. PMID: 26638028, PMCID: PMC4696904, DOI: 10.1016/j.cyto.2015.11.021.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorWNV encephalitisWest Nile virusHigh-expression MIF allelesWest Nile virus encephalitisNeuroinvasive WNV diseaseCase-control studyMigration inhibitory factorNorth American patientsMIF locusWNV neuropathogenesisVirus encephalitisViral neuroinvasionInnate cytokinesMIF allelesAmerican patientsTherapeutic targetAnimal modelsWNV diseaseEncephalitisInhibitory factorFunctional polymorphismsPatientsNile virusImportant determinant
2014
IL-6 Receptor α Defines Effector Memory CD8+ T Cells Producing Th2 Cytokines and Expanding in Asthma
Lee N, You S, Shin MS, Lee WW, Kang KS, Kim SH, Kim WU, Homer RJ, Kang MJ, Montgomery RR, Dela Cruz CS, Shaw AC, Lee PJ, Chupp GL, Hwang D, Kang I. IL-6 Receptor α Defines Effector Memory CD8+ T Cells Producing Th2 Cytokines and Expanding in Asthma. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 1383-1394. PMID: 25390970, PMCID: PMC4299645, DOI: 10.1164/rccm.201403-0601oc.Peer-Reviewed Original ResearchConceptsEffector memory CD8EM CD8T cellsPeripheral bloodMemory CD8IL-13IL-5IL-6RαTh2-type cytokine IL-5Different T cell subsetsLevels of GATA3Frequency of ILT cell subsetsTh2-type cytokinesHealthy control subjectsRespiratory syncytial virusT cell populationsCytokines IL-5IL-6 receptor αIL-6Rα expressionHuman peripheral bloodEffector CD8Syncytial virusTh2 cytokinesCell subsetsSystems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cellsHuman monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling
Lee N, Shin MS, Kang KS, Yoo SA, Mohanty S, Montgomery RR, Shaw AC, Kang I. Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling. Clinical Immunology 2014, 152: 101-110. PMID: 24657713, PMCID: PMC4018768, DOI: 10.1016/j.clim.2014.03.003.Peer-Reviewed Original ResearchImmune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2013
Functional Polymorphisms in the Gene Encoding Macrophage Migration Inhibitory Factor Are Associated With Gram-Negative Bacteremia in Older Adults
Das R, Subrahmanyan L, Yang IV, van Duin D, Levy R, Piecychna M, Leng L, Montgomery RR, Shaw A, Schwartz DA, Bucala R. Functional Polymorphisms in the Gene Encoding Macrophage Migration Inhibitory Factor Are Associated With Gram-Negative Bacteremia in Older Adults. The Journal Of Infectious Diseases 2013, 209: 764-768. PMID: 24158957, PMCID: PMC3923543, DOI: 10.1093/infdis/jit571.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorLow expressionOlder adultsInhibitory factorSurface Toll-like receptor 4Toll-like receptor 4Gram-negative bacteremiaPeripheral blood monocytesNegative bacterial infectionsMIF productionImmune mediatorsNegative bacteremiaHealthy controlsReceptor 4Blood monocytesOlder subjectsBacterial infectionsFunctional polymorphismsHigh expressionBacteremiaAdultsExpressionPatientsCohortCytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis
Reis EA, Hagan JE, Ribeiro GS, Teixeira-Carvalho A, Martins-Filho OA, Montgomery RR, Shaw AC, Ko AI, Reis MG. Cytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis. PLOS Neglected Tropical Diseases 2013, 7: e2457. PMID: 24069500, PMCID: PMC3777885, DOI: 10.1371/journal.pntd.0002457.Peer-Reviewed Original ResearchConceptsSevere pulmonary hemorrhage syndromeIL-10IL-6Mild diseaseClinical outcomesIL-8Disease progressionSevere diseaseSerum cytokine responseDays of symptomsHospital-based surveillanceAnti-inflammatory cytokinesIL-6 levelsCase-control study designPulmonary hemorrhage syndromeSevere clinical outcomesMultiplex bead array assayNon-fatal casesLife-threatening outcomesBead array assayImmunopathogenic roleCytokine profileCytokine stormIL-17ANonfatal outcomes